A 48-year-old woman from Mumbai with a 10-year history of recurrent epigastric pain and dyspepsia is found to be Helicobacter pylori-positive on serology. What is the most common cause of peptic ulcer disease worldwide?

Question

Accepted Answer

D. Helicobacter pylori infection. ## Etiology of Peptic Ulcer Disease: Global Perspective

**Key Point:** Helicobacter pylori infection is the most common cause of peptic ulcer disease worldwide, accounting for approximately 60–90% of all peptic ulcers (duodenal and gastric combined).

### Epidemiology and Pathophysiology

**High-Yield:** H. pylori prevalence varies by geography:
- **Developing countries (including India)**: 40–60% of the population
- **Developed countries**: 10–30% of the population
- **Among peptic ulcer patients**: 60–90% are H. pylori-positive

### Mechanism of H. pylori-Induced Ulceration

1. **Colonization**: H. pylori adheres to gastric mucosa via flagella and adhesins (BabA, SabA).
2. **Inflammation**: Triggers chronic active gastritis with infiltration of neutrophils, lymphocytes, and plasma cells.
3. **Acid dysregulation**: Increases gastric acid secretion (especially in duodenal ulcers) and reduces bicarbonate secretion.
4. **Mucosal damage**: Bacterial urease and proteases directly damage the mucosa; ammonia produced by urease is cytotoxic.
5. **Ulcer formation**: Loss of mucosal integrity leads to ulceration, typically in the antrum (gastric ulcers) or duodenum (duodenal ulcers).

### Comparative Etiology Table

| Cause | Frequency (%) | Geographic Notes | Clinical Features |
|-------|---------------|------------------|-------------------|
| H. pylori | 60–90 | Highest in developing countries; endemic in India | Chronic gastritis, both gastric and duodenal ulcers |
| NSAIDs | 10–25 | Higher in elderly, developed countries | Acute presentation; gastric ulcers > duodenal |
| Zollinger-Ellison | <1 | Rare; associated with MEN-1 | Multiple/refractory ulcers; severe diarrhea |
| Stress ulcers | <5 | ICU patients, severe burns, trauma | Acute erosions; superficial |
| Idiopathic | 5–10 | Declining with H. pylori screening | Diagnosis of exclusion |

**Clinical Pearl:** In India and other developing nations, H. pylori is the dominant cause. The introduction of H. pylori eradication therapy has dramatically reduced peptic ulcer incidence in countries with effective screening and treatment programs.

**Warning:** Do not confuse H. pylori prevalence in the general population with its role in peptic ulcer disease. While 40–50% of Indians harbor H. pylori, only a subset develop ulcers (lifetime risk ~15–20% of infected individuals).

**Mnemonic:** **HELP** — H. pylori, Erosive (NSAIDs), Lifestyle (stress, smoking), Pathologic (Zollinger-Ellison).

Answer

A. Zollinger-Ellison syndrome

Answer

B. Severe physiological stress

Answer

C. Nonsteroidal anti-inflammatory drug (NSAID) use

A 48-year-old woman from Mumbai with a 10-year history of recurrent epigastric pain and dyspepsia is found to be Helicobacter pylori-positive on serology. What is the most common cause of peptic ulcer disease worldwide?

Explanation

Etiology of Peptic Ulcer Disease: Global Perspective

Epidemiology and Pathophysiology

Mechanism of H. pylori-Induced Ulceration

Comparative Etiology Table

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Cause	Frequency (%)	Geographic Notes	Clinical Features
H. pylori	60–90	Highest in developing countries; endemic in India	Chronic gastritis, both gastric and duodenal ulcers
NSAIDs	10–25	Higher in elderly, developed countries	Acute presentation; gastric ulcers > duodenal
Zollinger-Ellison	<1	Rare; associated with MEN-1	Multiple/refractory ulcers; severe diarrhea
Stress ulcers	<5	ICU patients, severe burns, trauma	Acute erosions; superficial
Idiopathic	5–10	Declining with H. pylori screening	Diagnosis of exclusion